Distribution of alpha(1)-adrenoceptor subtype mRNA and identification of subtype responsible for renovascular contraction in human renal artery

This study was intended to quantify the amounts of the alpha(1)-adrenocepto r subtype mRNAs in human renal artery and to demonstrate the distribution o f receptor subtypes responsible for the contraction of the renal artery. RN ase protection assay showed that the mean amount of alpha(1a) mRNA was much greater than that of alpha(1b) or alpha(1d) mRNAs in both the main and bra nch renal arteries. However, the abundance of alpha(1a) mRNA in human renal artery was much less than in our previous data in the prostate (18,19). In situ hybridization showed that all a, subtype mRNAs were localized in the smooth muscle cells of the tunica media of the artery, and the distribution pattern of these three mRNAs in the main artery was the same as in the bra nch artery. However, the intensity of signals for alpha(1d) and alpha(1b) a ntisense RNAs probes was lower than that for the alpha(1a) antisense RNA pr obe. In the functional study, concentration-response curves to noradrenalin e pretreated with KMD-3213, an alpha(1A/L)-adrenoceptor selective antagonis t, seemed to be biphasic in nature. Chloroethyclonidine (CEC) failed to ina ctivate the noradrenaline-induced contraction, and prazosin skewed relative ly low affinity with a pA(2) value of 8.8. These data suggest that the alph a(1A/L)- adrenoceptor mediates primarily those responses to noradrenaline i n this artery. The other alpha(1)-adrenoceptor subtypes could also mediate the secondary contractile response to noradrenaline in this artery.